The largest-ever set of human genomes from a single population and the consequent insights into mutation, evolution, gene function and disease predisposition are reported in four linked papers. These results provide a strategy for the analysis of the full spectrum of genetic variation in any population and raise questions about how society should implement the knowledge gained.
Produced with support from Illumina.
Letters
Identification of a large set of rare complete human knockouts
Patrick Sulem, Hannes Helgason, Asmundur Oddson, Hreinn Stefansson, Sigurjon A Gudjonsson, Florian Zink, Eirikur Hjartarson, Gunnar Th Sigurdsson, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Olafur Th Magnusson, Augustine Kong, Agnar Helgason, Hilma Holm, Unnur Thorsteinsdottir, Gisli Masson, Daniel F Gudbjartsson & Kari Stefansson
doi:10.1038/ng.3243
Nature Genetics, published online: March 25, 2015
Patrick Sulem, Hannes Helgason and colleagues identify homozygous and compound heterozygous loss-of-function variants of minor allele frequency <2% in 7.7% of the genotyped Icelandic population. Under transmission of some of these variants from heterozygous parents provides evidence that they are actually deleterious.
The Y-chromosome point mutation rate in humans
Agnar Helgason, Axel W Einarsson, Valdis B Gudmundsdottir, Asgeir Sigurdsson, Ellen D Gunnarsdottir, Anuradha Jagadeesan, S Sunna Ebenesersdottir, Augustine Kong & Kari Stefansson
doi:10.1038/ng.3171
Nature Genetics, published online: March 25, 2015
Agnar Helgason and colleagues report the point mutation rate for the male-specific euchromatic sequence of the Y chromosome based on 753 Icelandic males. They find that the non-recombining portions of the Y chromosome mutate at a faster rate than palindromic regions, suggesting that gene conversion acts to correct mutations in palindromic sequences.
Article
Large-scale whole-genome sequencing of the Icelandic population
Daniel F Gudbjartsson, Hannes Helgason, Sigurjon A Gudjonsson, Florian Zink, Asmundur Oddson, Arnaldur Gylfason, Soren Besenbacher, Gisli Magnusson, Bjarni V Halldorsson, Eirikur Hjartarson, Gunnar Th Sigurdsson, Simon N Stacey, Michael L Frigge, Hilma Holm, Jona Saemundsdottir, Hafdis Th Helgadottir, Hrefna Johannsdottir, Gunnlaugur Sigfusson, Gudmundur Thorgeirsson, Jon Th Sverrisson, Solveig Gretarsdottir, G Bragi Walters, Thorunn Rafnar, Bjarni Thjodleifsson, Einar S Bjornsson, Sigurdur Olafsson, Hildur Thorarinsdottir, Thora Steingrimsdottir, Thora S Gudmundsdottir, Asgeir Theodors, Jon G Jonasson, Asgeir Sigurdsson, Gyda Bjornsdottir, Jon J Jonsson, Olafur Thorarensen, Petur Ludvigsson, Hakon Gudbjartsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, David O Arnar, Olafur Th Magnusson, Augustine Kong, Gisli Masson, Unnur Thorsteinsdottir, Agnar Helgason, Patrick Sulem & Kari Stefansson
doi:10.1038/ng.3247
Nature Genetics, published online: March 25, 2015
Kari Stefansson and colleagues report the whole-genome sequencing of 2,636 individuals from Iceland to a median of 20× coverage, providing a valuable genomic resource for this population isolate. They characterize patterns of genetic variation and population structure and demonstrate the usefulness of this resource for genetic discovery for several disease phenotypes.
Brief Communication
Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease
Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson, Hrefna Johannsdottir, Andres Ingason, Hannes Helgason, Patrick Sulem, Olafur Th Magnusson, Sigurjon A Gudjonsson, Unnur Unnsteinsdottir, Augustine Kong, Seppo Helisalmi, Hilkka Soininen, James J Lah, Ina Selseth Almdahl, Fred Andersen, Nenad Bogdanovic, Anne Brækhus, Knut Engedal, Arvid Rongve, Ingvild Saltvedt, Eystein Stordal & Aree Witoelar for DemGene, Dag Aarsland, Tormod Fladby, Ingun D Ulstein, Srdjan Djurovic, Sigrid B Sando, Linda R White, Gun-Peggy Knudsen, Lars T Westlye, Geir Selbæk, Ina Giegling, Harald Hampel, Mikko Hiltunen, Allan I Levey, Ole A Andreassen, Dan Rujescu, Palmi V Jonsson, Sigurbjorn Bjornsson, Jon Snaedal & Kari Stefansson
doi:10.1038/ng.3246
Nature Genetics, published online: March 25, 2015
Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States.
Data Descriptor
Sequence variants from whole genome sequencing a large group of Icelanders
Daniel F. Gudbjartsson, Patrick Sulem, Hannes Helgason, Arnaldur Gylfason, Sigurjon A. Gudjonsson, Florian Zink, Asmundur Oddson, Gisli Magnusson, Bjarni V. Halldorsson, Eirikur Hjartarson, Gunnar Th. Sigurdsson, Augustine Kong, Agnar Helgason, Gisli Masson, Olafur Th. Magnusson, Unnur Thorsteinsdottir & Kari Stefansson
doi:10.1038/sdata.2015.11
Scientific Data, published online: March 25, 2015
Daniel F. Gudbjartsson et al. describe the genesis of the sequence data from the Icelandic population, the resources available and the conditions for data access under Icelandic law.
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